Expert Opinion on Therapeutic Targets最新文献_第2页

Progress and challenges in glypican-3 targeting for hepatocellular carcinoma therapy. 以 glypican-3 为靶点治疗肝细胞癌的进展与挑战。

IF 5.4 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-10-01 Epub Date: 2024-10-20 DOI: 10.1080/14728222.2024.2416975

Arnaud Couzinet, Toshihiro Suzuki, Tetsuya Nakatsura

{"title":"Progress and challenges in glypican-3 targeting for hepatocellular carcinoma therapy.","authors":"Arnaud Couzinet, Toshihiro Suzuki, Tetsuya Nakatsura","doi":"10.1080/14728222.2024.2416975","DOIUrl":"10.1080/14728222.2024.2416975","url":null,"abstract":"Introduction: Glypican-3 (GPC3) is a cell membrane-anchored heparan sulfate proteoglycan that has recently garnered attention as a cancer antigen owing to its high expression in numerous cancers, particularly hepatocellular carcinoma (HCC), and to limited expression in adult normal tissue.Areas covered: Here, we propose the potential of GPC3 as a cancer antigen based on our experience with the GPC3 peptide vaccine against HCC, having developed a vaccine that progressed from preclinical studies to first-in-human clinical trials. In this review, we present a summary of the current status and future prospects of immunotherapies targeting GPC3 by focusing on clinical trials; peptide vaccines, mRNA vaccines, antibody therapy, and chimeric antigen receptor/T-cell receptor - T-cell therapy and discuss additional strategies for effectively eliminating HCC through immunotherapy.Expert opinion: GPC3 is an ideal cancer antigen for HCC immunotherapy. In resectable HCC, immunotherapies that leverage physiological immune surveillance, immune checkpoint inhibitors, and GPC3-target cancer vaccines appear promising in preventing recurrence and could be considered as a prophylactic adjuvant therapy. However, in advanced HCC, clinical trials have not demonstrated sufficient anti-tumor efficacy, in contrast with preclinical studies. Reverse translation, bedside-to-bench research, is crucial to identify the factors that have hindered GPC3 target immunotherapies.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"895-909"},"PeriodicalIF":5.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

What is holding back preclinical GPR119 agonists from their potential as the therapeutics of type 2 diabetes? 是什么阻碍了临床前 GPR119 激动剂发挥治疗 2 型糖尿病的潜力？

IF 5.4 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-10-01 Epub Date: 2024-10-29 DOI: 10.1080/14728222.2024.2421751

Jing Hu, Yu Cao, Lianxiang Duan, Jinghua Peng

引用次数: 0

Targeting the TRPV1 pain pathway in osteoarthritis of the knee. 针对膝骨关节炎的 TRPV1 疼痛通路。

IF 5.4 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-10-01 Epub Date: 2024-10-25 DOI: 10.1080/14728222.2024.2416961

Ali Mobasheri, François Rannou, Stefan Ivanavicius, Philip G Conaghan

{"title":"Targeting the TRPV1 pain pathway in osteoarthritis of the knee.","authors":"Ali Mobasheri, François Rannou, Stefan Ivanavicius, Philip G Conaghan","doi":"10.1080/14728222.2024.2416961","DOIUrl":"10.1080/14728222.2024.2416961","url":null,"abstract":"Introduction: The growing prevalence and lack of effective pain therapies for knee osteoarthritis (KOA) results in a substantial unmet need for novel analgesic therapies. The transient receptor potential vanilloid 1 (TRPV1) receptor is expressed in subsets of nociceptive sensory neurons and has major roles in pain transmission and regulation. In the structures of the knee joint, nociceptors are present in abundance.Areas covered: TRPV1-expressing nociceptors in the knee represent a rational target to modulate activity at the origin of the pain pathway in KOA and may avoid systemic side effects seen with currently available analgesics. TRPV1 antagonists can induce analgesia, but hyperthermia and thermal hypesthesia side effects have limited their utility. Clinical development of TRPV1 agonists for pain management has progressed further than that of TRPV1 antagonists. Capsaicin and resiniferatoxin have provided proof-of-concept for the modulation of TRPV1 activity in KOA.Expert opinion: Intra-articular administration of TRPV1 agonists enables direct delivery to target nerve terminals in the knee, offering a potentially transformative approach for the management of pain associated with KOA. Here, we explore the advances in understanding innervation of the knee joint in KOA, the role of TRPV1-expressing neurons and progress in developing TRPV1 modulators for KOA.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"843-856"},"PeriodicalIF":5.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expression of Concern: Overexpression of HMGA2 in breast cancer promotes cell proliferation, migration, invasion and stemness. 关注表达：乳腺癌中 HMGA2 的过表达会促进细胞增殖、迁移、侵袭和干性。

IF 5.4 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-10-01 Epub Date: 2024-10-21 DOI: 10.1080/14728222.2024.2417515

引用次数: 0

The role of Nrf2 in immune cells and inflammatory autoimmune diseases: a comprehensive review. Nrf2 在免疫细胞和炎症性自身免疫疾病中的作用：全面综述。

IF 5.8 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-09-10 DOI: 10.1080/14728222.2024.2401518

Wang-Dong Xu,Chan Yang,An-Fang Huang

{"title":"The role of Nrf2 in immune cells and inflammatory autoimmune diseases: a comprehensive review.","authors":"Wang-Dong Xu,Chan Yang,An-Fang Huang","doi":"10.1080/14728222.2024.2401518","DOIUrl":"https://doi.org/10.1080/14728222.2024.2401518","url":null,"abstract":"INTRODUCTIONNrf2 regulates mild stress, chronic inflammation, and metabolic changes by regulating different immune cells via downstream signaling. Collection of information about the role of Nrf2 in inflammatory autoimmune diseases will better understand the therapeutic potential of targeting Nrf2 in these diseases.AREAS COVEREDIn this review, we comprehensively discussed biological function of Nrf2 in different immune cells, including Nrf2 preventing oxidative tissue injury, affecting apoptosis of immune cells and inflammatory cytokine production. Moreover, we discussed the role of Nrf2 in the development of inflammatory autoimmune diseases.EXPERT OPINIONNrf2 binds to downstream signaling molecules and then provides durable protection against different cellular and organ stress. It has emerged as an important target for inflammatory autoimmune diseases. Development of Nrf2 modulator drugs needs to consider factors such as target specificity, short/long term safety, disease indication identification, and the extent of variation in Nrf2 activity. We carefully discussed the dual role of Nrf2 in some diseases, which helps to better target Nrf2 in the future.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":"12 1","pages":"1-18"},"PeriodicalIF":5.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Can we target insulin signalling for cognition therapeutics? 我们能否针对胰岛素信号进行认知治疗？

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-09-01 Epub Date: 2024-09-24 DOI: 10.1080/14728222.2024.2407821

Simone Macrì, Giovanni Laviola

引用次数: 0

Combined cancer immunotherapy based on targeting adenosine pathway and PD-1/PDL-1 axis. 以腺苷通路和 PD-1/PDL-1 轴为靶点的联合癌症免疫疗法。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-09-01 Epub Date: 2024-09-20 DOI: 10.1080/14728222.2024.2405090

Mehrdad Fathi, Asieh Zarei, Ata Moghimi, Pooya Jalali, Zahra Salehi, Sharareh Gholamin, Farhad Jadidi-Niaragh

{"title":"Combined cancer immunotherapy based on targeting adenosine pathway and PD-1/PDL-1 axis.","authors":"Mehrdad Fathi, Asieh Zarei, Ata Moghimi, Pooya Jalali, Zahra Salehi, Sharareh Gholamin, Farhad Jadidi-Niaragh","doi":"10.1080/14728222.2024.2405090","DOIUrl":"10.1080/14728222.2024.2405090","url":null,"abstract":"Introduction: Cancer immunotherapy has revolutionized the field of oncology, offering new hope to patients with advanced malignancies. Tumor-induced immunosuppression limits the effectiveness of current immunotherapeutic strategies, such as PD-1/PDL-1 checkpoint inhibitors. Adenosine, a purine nucleoside molecule, is crucial to this immunosuppression because it stops T cells from activating and helps regulatory T cells grow. Targeting the adenosine pathway and blocking PD-1/PDL-1 is a potential way to boost the immune system's response to tumors.Areas covered: This review discusses the current understanding of the adenosine pathway in tumor immunology and the preclinical and clinical data supporting the combination of adenosine pathway inhibitors with PD-1/PDL-1 blockade. We also discuss the challenges and future directions for developing combination immunotherapy targeting the adenosine pathway and the PD-1/PDL-1 axis for cancer treatment.Expert opinion: The fact that the adenosine signaling pathway controls many immune system processes suggests that it has a wide range of therapeutic uses. Within the next five years, there will be tremendous progress in this area, and the standard of care for treating malignant tumors will have switched from point-to-point therapy to the integration of immunological networks comprised of multiple signaling pathways, like the adenosine axis.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"757-777"},"PeriodicalIF":4.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic indications for HDAC6 inhibitors in the peripheral and central nervous disorders. HDAC6 抑制剂在外周和中枢神经疾病中的治疗适应症。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-09-01 Epub Date: 2024-09-20 DOI: 10.1080/14728222.2024.2404571

Jonathan van Eyll, Robert Prior, Sylvain Celanire, Ludo Van Den Bosch, Frederik Rombouts

{"title":"Therapeutic indications for HDAC6 inhibitors in the peripheral and central nervous disorders.","authors":"Jonathan van Eyll, Robert Prior, Sylvain Celanire, Ludo Van Den Bosch, Frederik Rombouts","doi":"10.1080/14728222.2024.2404571","DOIUrl":"10.1080/14728222.2024.2404571","url":null,"abstract":"Introduction: Inhibition of the enzymatic function of HDAC6 is currently being explored in clinical trials ranging from peripheral neuropathies to cancers. Advances in selective HDAC6 inhibitor discovery allowed studying highly efficacious brain penetrant and peripheral restrictive compounds for treating PNS and CNS indications.Areas covered: This review explores the multifactorial role of HDAC6 in cells, the common pathological hallmarks of PNS and CNS disorders, and how HDAC6 modulates these mechanisms. Pharmacological inhibition of HDAC6 and genetic knockout/knockdown studies as a therapeutic strategy in PNS and CNS indications were analyzed. Furthermore, we describe the recent developments in HDAC6 PET tracers and their utility in CNS indications. Finally, we explore the advancements and challenges with HDAC6 inhibitor compounds, such as hydroxamic acid, fluoromethyl oxadiazoles, HDAC6 degraders, and thiol-based inhibitors.Expert opinion: Based on extensive preclinical evidence, pharmacological inhibition of HDAC6 is a promising approach for treating both PNS and CNS disorders, given its involvement in neurodegeneration and aging-related cellular processes. Despite the progress in the development of selective HDAC6 inhibitors, safety concerns remain regarding their chronic administration in PNS and CNS indications, and the development of novel compound classes and modalities inhibiting HDAC6 function offer a way to mitigate some of these safety concerns.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"719-737"},"PeriodicalIF":4.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Innovations in treating acute graft-versus-host disease: a review of preclinical targets and strategies. 治疗急性移植物抗宿主疾病的创新：临床前靶点和策略综述。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-09-01 Epub Date: 2024-09-19 DOI: 10.1080/14728222.2024.2405091

Haoliang Duan, Yuhua Ru, Jia Chen

{"title":"Innovations in treating acute graft-versus-host disease: a review of preclinical targets and strategies.","authors":"Haoliang Duan, Yuhua Ru, Jia Chen","doi":"10.1080/14728222.2024.2405091","DOIUrl":"10.1080/14728222.2024.2405091","url":null,"abstract":"Introduction: Acute graft-versus-host disease (aGVHD) is a major complication of post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) that severely impacts patient survival and quality of life. Despite advancements in standard care, therapeutic outcomes remain suboptimal, necessitating the exploration of innovative strategies.Areas covered: This review synthesizes preclinical research focusing on novel therapeutic targets and strategies that may enhance treatment efficacy. We critically analyzed the role of specific T-cell subsets, cytokine modulators, and intracellular signaling pathways in reducing aGVHD severity. Emphasis is placed on experimental findings that illuminate the mechanisms of immune tolerance and survival improvement. We discuss the translation of these findings into potential clinical trials and evaluate the challenges and progress in implementing these strategies, including scalability and impact on the graft-versus-leukemia (GVL) effect.Expert opinion: Our review summarizes the latest therapeutic targets and strategies in preclinical research for aGVHD, aiming to bridge the gap between clinical and experimental medicine. By integrating immunology, genetics, and cytology, we seek to enhance the translation of preclinical findings into clinical strategies. This multidisciplinary approach is expected to improve patient outcomes in aGVHD treatment, ultimately leading to more effective and safer therapies.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"807-824"},"PeriodicalIF":4.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The endocannabinoid system as a therapeutic target in neuropathic pain: a review. 内源性大麻素系统作为神经性疼痛的治疗靶点：综述。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2024-09-01 Epub Date: 2024-09-24 DOI: 10.1080/14728222.2024.2407824

Jose-Manuel Quintero, Luis-Eduardo Diaz, Ismael Galve-Roperh, Rosa-Helena Bustos, Marta-Ximena Leon, Stephania Beltran, Seetal Dodd

{"title":"The endocannabinoid system as a therapeutic target in neuropathic pain: a review.","authors":"Jose-Manuel Quintero, Luis-Eduardo Diaz, Ismael Galve-Roperh, Rosa-Helena Bustos, Marta-Ximena Leon, Stephania Beltran, Seetal Dodd","doi":"10.1080/14728222.2024.2407824","DOIUrl":"https://doi.org/10.1080/14728222.2024.2407824","url":null,"abstract":"Introduction: This review highlights the critical role of the endocannabinoid system (ECS) in regulating neuropathic pain and explores the therapeutic potential of cannabinoids. Understanding the mechanisms of the ECS, including its receptors, endogenous ligands, and enzymatic routes, can lead to innovative treatments for chronic pain, offering more effective therapies for neuropathic conditions. This review bridges the gap between preclinical studies and clinical applications by emphasizing ECS modulation for better pain management outcomes.Areas covered: A review mapped the existing literature on neuropathic pain and the effects of modulating the ECS using natural and synthetic cannabinoids. This analysis examined ECS components and their alterations in neuropathic pain, highlighting the peripheral, spinal, and supraspinal mechanisms. This review aimed to provide a thorough understanding of the therapeutic potential of cannabinoids in the management of neuropathic pain.Expert opinion: Advances in cannabinoid research have shown significant potential for the management of chronic neuropathic pain. The study emphasizes the need for high-quality clinical trials and collaborative efforts among researchers, clinicians, and regulatory bodies to ensure safe and effective integration of cannabinoids into pain management protocols. Understanding the mechanisms and optimizing cannabinoid formulations and delivery methods are crucial for enhancing therapeutic outcomes.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":"28 9","pages":"739-755"},"PeriodicalIF":4.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0